What is the evidence that mammals are unable to process excess sodium chloride?

What is the evidence that mammals are unable to process excess sodium chloride?

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I grew up hearing the mantra

excess salt causes heart disease

I had a vague understanding that it caused deposits in the body or something. Now that I give it more thought - I come up with three vaguely plausible explanations for this:

  • kidneys have a fixed limit on how much sodium chloride they can filter from your bloodstream in a day
  • excess salt has an effect on oxidation/redux reactions or acid/base levels that means your body's chemical reactions aren't performing optimally
  • the excess ions mess with other reactions in the body

When I take the 'devils advocate' argument in my mind - my plausible arguments are:

  • how can salt cause deposits in the body? It would simply dissolve in the bloodstream
  • surely the body has sufficient chemical mechanism to flush out surplus sodium ions

Now the author here makes the following claim:

The entire field of research around salt is a colossal [stuffup], for a fairly simple reason: sweat is salty. If you sweat, due to exercise or high temperatures, you lose about 1g/L of sodium. So right off the bat, all the research that's trying to find a population-wide correct amount of sodium to eat is on a wrong track, because there's no such thing.

But it's even worse, because most of the research doesn't measure the amount of sodium people take in through food, it measures the amount of sodium they lose in urine. This isn't their intake, it's what's left after losses, so it's confounded by exercise.

And it's even worse than that, because while the actual studies indicate that there's no benefit from cutting salt intake, some high-status organizations once said there was, and are acting as though they can't take it back without losing face.

The overall result is that there are a bunch of people shouting "less salt!" and a bunch of people shouting "the same amount of salt!" and no one has any model of how much salt they actually need, so they occasionally end up deficient.

In addition, the article here claims:

… there are the epidemiologists whose research appears to point in the other direction. They track the connection between salt and deaths from heart attacks and strokes, and their studies indicate that while heavy salt eaters did die sooner, there is little evident danger from the average American's intake.

My question is: What is the evidence that mammals are unable to process excess sodium chloride?

Homeostasis: Osmoregulation PPQs

In 24 hours, a person excreted 1660 mg of creatinine in his urine. The concentration of creatinine in the blood entering his kidneys was constant at 0.01 mg cm-3.

Big molecules e.g. protein, red blood cells stay in the blood

Small molecules e.g. urea, water, glucose enter the

Selective reabsorption takes place in the proximal/first convoluted tubule

Useful substances e.g. glucose that were filtered out of the blood are reabsorbed back in to the blood

Causes ultrafiltration at Bowman's capsule / glomeruli / renal capsule

Through basement membrane

Enabled by small size urea molecule

At the PCT / descending LoH

Active transport of ions / glucose creates gradient

Small molecules / named example

Pass through basement membrane / basement membrane acts as filter

Protein too large to go through / large so stays behind

High concentration in tubule / in filtrate

Reabsorbed by facilitated diffusion / active transport

Requires proteins / carriers

These are working at maximum rate / are saturated

Not all glucose is reabsorbed / some is lost in urine

From collecting duct / from end of second convoluted tubule

Due to longer loop of Henle

Sodium / chloride ions absorbed from filtrate in ascending limb

Gradient established in medulla / concentration of ions increases down

Acts on collecting duct / distal convoluted tubule / second convoluted


the potential difference/voltage obtained when a half-cell is connected to a standard hydrogen electrode

the electrons flow from the half-cell to the standard hydrogen electrode / the half-cell forms the negative electrode when connected to the standard half-cell / Fe is a better reducing agent than (<< ext>_2>) / Fe is above (<< ext>_2>) in electrochemical series

Accept &ldquothe half reaction is not spontaneous&rdquo.

correct diagram including voltmeter

No credit if wires to electrodes immersed in the solutions.

Do not accept name of salt (e.g. potassium nitrate) in place of salt bridge.

correctly labelled (+) and (&ndash) electrodes / cathode and anode

flow of electrons from Fe to Ag in external circuit

Award [2 max]if battery shown instead of voltmeter.

(the solution changes) from orange to green

Do not accept 6, 6+ or the use of Roman numerals unless they have already been penalized in (2)(a).

For second equation award [1]for correct reactants and products and [1]for correct balancing.

sodium is a very powerful reducing agent/high in electrochemical series

any chemical reducing agent would need to be even higher in ECS to reduce (< ext><< ext>^ + >) / OWTTE

hydrogen is below Na in ECS

if sodium were to be formed it would react with the water in the solution / OWTTE

Modeling in FW fish

Some energetic considerations

For TW-adapted fish, ΔΨ varies substantially and is especially sensitive to environmental [Ca 2+ ](Eddy, 1975 Potts, 1984). If[Ca 2+ ] is <1 mmol l –1 , ΔΨ in 1 mmol l –1 Na + would be approximately –5 mV to–10 mV (outside solution reference). If extracellular fluid (ECF)[Na + ] is ∼150 mmol l –1 , equation 1 shows that the cost of transport is ∼11.3 kJ eq –1 . Since three Na + are transferred per mole ATP used, the cost of one cycle of the pump is just over 34 kJ. The energy released by ATP hydrolysis in a cycle is∼63 kJ (the data are from frog skin Civan et al., 1983). Assuming that the free energy yield is similar in fish gill, the Na + /K + -ATPase would be operating at <60% efficiency and could handle the energy requirement without calling on another source.

The alternative situation is for a FW animal maintaining a steady state atμmol l –1 Na + concentrations (i.e. SD animals). The crayfish C. destructor maintained a steady state in[Na + ]≈50 μmol l –1 . Hemolymph[Na + ] was ∼190 mmol l –1 , and ΔΨ was 10.3 mV. From equation 1, the energy barrier is 21 kJ eq –1 ,and hence 63 kJ per ATPase cycle. This equals the free energy released by ATP hydrolysis and, since 100% efficiency is unlikely, a second energy source is required we might expect this to be the proton ATPase.

Experimental approaches

Krogh had suggested that, since Na + was absorbed from salts of impermeant anions, it might be exchanged for NH4 + . This theme was proposed again when it was shown that net Na + uptake was roughly equal to NH4 + efflux in crayfish(Shaw, 1960a). It was extended to fish (the goldfish Carassius auratus) a few years later when it was shown, in agreement with Krogh, that Na + uptake occurred in the absence of anion absorption(Garcia Romeu and Maetz, 1964)and that injection of NH4 + into the body fluids stimulated Na + influx, while elevating [NH4 + ]in the bathing medium reduced it (Maetz and Garcia Romeu, 1964). Obviously, a Na + /NH4 + exchange at the apical membrane is very different from the events described by the frog skin model. However, the proposal became controversial within a short time. For example, it was shown that when the experimental design engendered changes in

The debate appeared to be ended with publication of experiments on a perfused trout (Salmo gairdneri) head(Avella and Bornancin, 1989)and intact rainbow trout (Oncorhynchus mykiss Wilson et al., 1994). In the former, it was shown that variations in

Two mechanisms have been proposed to account for an Na + /H + exchange in fish. The first, an exchange protein in the apical membrane of cells in the gill, has a long history, perhaps because the Michaelis–Menten concentration dependence suggested the combination of Na + with a membrane protein. However, it was argued that such a neutral exchanger could not take advantage of the membrane potential and that the proton and sodium gradients were insufficient to drive the exchange (Avella and Bornancin,1989). This is probably true but hard to demonstrate, since intracellular [Na + ] values are uncertain in fish gills. Several measurements have produced wildly disparate values, from approximately 10 mmol l –1 to 80 mmol l –1 (Li et al., 1997 Morgan et al., 1994 Eddy and Chang, 1993 Wood and LeMoigne, 1991). In frog skin (PCs) bathed with 1 mmol l –1 Na on the apical surface, [Na + ]cell was ∼4 mmol l –1 ,and this might serve as a likely benchmark for FW vertebrate transport epithelia. Intracellular pH is also uncertain in fish gill. It has been measured only in rainbow trout, where it was 7.3–7.4(Wood and LeMoigne, 1991 Goss and Wood, 1991).

Since the striking work on the frog skin model(Ehrenfeld et al., 1985), the proton pump–Na + channel has been proposed as the alternative mechanism underlying apical Na + /H + exchange in FW fish gills. It is worth examining current information about the presence,distribution and significance of each of the several components of this system.

The Na + /K + -ATPase

This transport enzyme is firmly established as the motor for Na + transport in most animal cells, and information regarding its presence in fish gills was summarized some time ago(DeRenzis and Bornancin,1984). The earliest study of its distribution showed that[ 3 H]ouabain binding in the killifish (Fundulus heteroclitus) adapted to 10% seawater (SW) was confined to MR cells in the filament (presumably interlamellar). Although lamellae were not shown, it was stated that respiratory cells [presumably pavement cells (PVCs)]“never exhibited the dense pattern of grains seen over chloride cells” (Karnaky et al.,1976). Labeling was much denser in SW-adapted animals,corresponding to the well-known marked increase in the enzyme in SW. More recently, the use of antibodies against a subunit of the enzyme has permitted its immunolocalization. In the rainbow trout, labeled cells were found on both the filament and the secondary lamellae but predominantly on the former(Witters et al., 1996). A similar pattern was seen in FW-adapted guppy (Poecilia reticulata Shikano and Fujio, 1998). Subsequently, the method was used in rainbow trout adapted to Vancouver, BC,Canada TW (very low [Na + ]), and the enzyme was found to be widely distributed on both the filament and lamellae. The pattern was similar but less intense for a fish adapted to Ottawa, ON, Canada TW, which also has low ion concentrations. The tilapia (Oreochromis mossambicus) also stained for the enzyme, but in this case predominantly on the filament and at the base of the lamellae (Wilson et al.,2000). Labeling occurred on both filament and lamellae in Oncorhynchus keta fry (Uchida et al., 1996), while in adults returning from SW (but adapted to FW)labeling was confined to cells on the lamellae(Uchida et al., 1997). In the FW-adapted stingray (Dasyatis sabina), the Na + /K + -ATPase was found in cells both on the lamellae and in the interlamellar region but was more numerous on the former(Piermarini and Evans, 2000, 2001).

A different approach to enzyme localization has also been described(Galvez et al., 2002). Gill cells from O. mykiss were disaggregated enzymatically and separated on a Percoll gradient into three fractions. Two of these were MR cells, as judged by fluorescent dye binding and labeling with an antibody to mitochondrial protein. One of the MR fractions bound peanut lectin agglutinin(PNA + ), while the other did not (PNA – ). It is interesting that the latter has the gross morphology of a PVC. Both MR cells had substantial amounts of the Na + /K + -ATPase in a PNA – :PNA + ratio of ∼0.3. When the fish was made hypercapnic (1% CO2), the ratio changed to ∼1.3. Unfortunately, because these data were expressed as a ratio, the change might indicate an increase in PNA – or a decrease in PNA + . However, either change would point to the PNA – cell as the pathway for

No consistent distribution pattern is apparent from these studies. Cells containing the enzyme occur on the filament in some, on the lamella in others and, especially in trout exposed to ion-poor water, in both regions. In addition, in most cases, labeled cells are described as `chloride cells'(without further identification), but in the trout in low ion water both chloride and pavement cells were labeled. This ambiguity is not trivial, since the enzyme should mark the pathway for

Carbonic anhydrase

Carbonic anhydrase is probably the first non-metabolic enzyme to be associated with epithelial ion transport. Based on reports of such a relationship in kidney and stomach, the effects of sulfonamide inhibitors of CA on Na + transport across isolated frog skin were assessed(Fuhrman, 1952). Only modest inhibition was achieved by high inhibitor concentrations. These experiments were run with Ringer solution bathing both sides of the skin and with the preparation short-circuited. Either condition uncouples

In the opercular epithelium of Fundulus heteroclitus adapted to FW, the enzyme was found largely in MR cells while PVCs had none(Lacy, 1983). The significance of this observation is not clear, since the isolated preparation, which is very active in SW-adapted fish, does not transport Na + in FW(Wood and Marshall, 1994 Marshall et al., 1997).

The proton ATPase

Having ruled out operation of an Na + /H + exchanger,Avella and Bornancin (1989)suggested that the proton pump–Na-channel model provides the mechanism for Na + /H + exchange in fish gill. This was later explored in rainbow trout by noting the effect of putative inhibitors of the H + -ATPase (vanadate, AZ) as well as amiloride on net proton efflux in rainbow trout. Vanadate and AZ both inhibited proton efflux (∼50%). However, vanadate is an inhibitor of P-ATPases (e.g. the Na + /K + enzyme) and does not affect V-ATPases(Forgac, 1989). In addition,proton efflux was unaffected by 0.1 mmol l –1 amiloride, which is known to inhibit net Na + uptake nearly completely, and even 1 mmol l –1 had only a modest effect(Lin and Randall, 1991). Their fig. 9 suggests that the frog skin model functions in fish gill, but vanadate data provide no support for the suggestion, and the apparent uncoupling of

Some recent studies have used immunohistochemistry to localize the enzyme in the gills of several FW fish. In O. mykiss gill, an antibody to the H + -ATPase was found along the lamellar surfaces generally concentrated in the apical regions. The conclusion was that both PVCs and MRCs were labeled (Lin et al.,1994). Another study in the same species found it localized to PVCs (Sullivan et al., 1995). This research group also used probes for the H + -ATPase mRNA to locate the mRNA and found it in the same cells. Hypercapnic acidosis augmented the mRNA signal as well as antibody staining(Sullivan et al., 1996). These observations suggest an increase in H + -ATPase during hypercapnia. This is consistent with one study showing that H + excretion increased in fish exposed to hypercapnia(Goss and Perry, 1993) but not with another in which it was unchanged(Perry et al., 1987). In addition,

Additional work examined antibody labeling patterns for several transport proteins in O. mossambicus and the rainbow trout. Those relevant to Na + uptake were the H + -ATPase, an Na + /H + exchanger, the Na + /K + -ATPase and ENaC. In both species, the H + -ATPase and Na channel were found together on lamellar PVCs. In the trout, the proteins were also found together but were more widely distributed than in the tilapia (Wilson et al., 2000). In a FW elasmobranch, the stingray Dasyatis sabina, the H + -ATPase and Na + /K + -ATPase were found on both interlamellar filaments and on the lamellae but in separate cells (Piermarini and Evans,2001). Moreover, the H + -ATPase was on the basolateral membrane and colocalized with a pendrin-based Cl – /HCO3 – exchanger on the apical membrane, suggestive of the βMR configuration. The Na + /K + -ATPase, in a different cell, was probably part of the system for absorbing Na + (Piermarini et al., 2002).

The cell isolation approach described above(Galvez et al., 2002) was also applied to locating the H + -ATPase. The ratio of PNA – :PNA + , for the enzyme in control animals, was∼2 and increased significantly during hypercapnia. This suggests that the Na + /K + -ATPase and the H + -ATPase are located in the same group of cells. Infusion of HCO3 – had no effect on the ratio.

Finally, bafilomycin (10 –5 mol l –1 )inhibited

The Na channel

The antibody study mentioned above(Wilson et al., 2000) showed that the channel occurred together with the H + -ATPase in the tilapia and rainbow trout. In a further examination of the PNA-separated MRCs,it was found that Na + entry into PNA – cells was substantial, even in the absence of a proton source. Addition of phenamil (an Na + channel blocker) had no effect on Na + movement, but 10 nmol l –1 bafilomycin inhibited the influx by ∼60%. Interpretation of these data is not obvious. However, when a proton source(proprionic acid) was added, the Na + influx increased by ∼50%,and the increase was inhibited by phenamil and even more by bafilomycin(Reid et al., 2003). Proton fluxes were not measured, but these inhibitor data suggest an Na + /H + exchange mediated by the Na channel–H + -ATPase couple. These observations support the suggestion that the PNA – cells are a (the?) route of Na + influx across the gill in rainbow trout.

In summary

These data show that key components of the frog skin model exist in the gills of several fish species, and it is reasonable to surmise that the system functions in sodium uptake and proton extrusion in at least some of them. However, the structure of the model and how it functions are still unknown. The path taken by Na + is still debated with some not very compelling evidence on both sides. The picture of how the components are distributed is far from uniform in the studies described above i.e. whether they occupy the same cells or are separated and connected only by a common APD. We have no secure knowledge of key intracellular variables that determine fluxes in the gill (concentrations and membrane potentials) nor can these be easily manipulated in order to test models. And, in most cases, we have only limited ability to control and manipulate the internal environment. What is lacking, of course, is a viable, functional, in vitro branchial preparation that allows such uncertainties to be addressed. The frog skin provided such a preparation and was used to generate convincing evidence for the model described earlier. The Fundulus opercular epithelium played a significant role in working out a model for NaCl transport in SW-adapted fish. For a time, it was hoped that this preparation, taken from FW-adapted animals, might play such a role for the FW gill. But, while it transports Cl – weakly, it does not transport Na + at all (by the flux ratio criterion Wood and Marshall, 1994 Marshall et al., 1997).

Since no natural, planar sheet of gill cells has come to light, attempts have been made to disaggregate the cells in a gill and grow them on solid,permeable supports in culture. It is hoped to produce, in this way, a functional transport system that can be addressed experimentally, as in the frog skin. Two preparations have been made. In one of these [single seeded insert (SSI)], the sheet consists solely of PVCs in the other [double seeded insert (DSI)], there are ∼85% PVCs and ∼15% MRCs. A comprehensive review of the behavior of these preparations has appeared(Wood et al., 2002). Briefly,some of the electrical and permeability characteristics resemble those of intact gill. However, neither preparation showed evidence of Na + transport. However, a recent study showed that when the cultured preparation was treated with cortisol there was evidence for weak active absorption of both Na + and Cl – (Zhou et al., 2003). The system is not yet a good model, since efflux of the ions greatly exceeds influx i.e. there was a large net loss of both.

An estuarine fish

Fundulus heteroclitus is estuarine and, while capable of hyperregulation in FW, it presents a picture incompatible with the Na channel–proton pump model. Sodium fluxes in FW are unusually high.

Cell Physiology of Pancreatic Ducts

Guanylin and Uroguanylin

Guanylin and uroguanylin are short peptides that exhibit a structural homology to Escherichia coli heat-stable entero-toxins (STA) (see Kulaksiz and colleagues [ 179 ]). In the gut, these peptides are present in enterochromaffin and mucous cells within the epithelium and are released luminally. Once in the lumen, they stimulate the guanylate cyclase C (GC-C) receptor on intestinal epithelial cells, leading to an increase in intracellular cyclic guanosine monophosphate (cGMP). The cGMP activates cGMP-dependent protein kinase (cGKII), which, in turn, phosphorylates CFTR to increase fluid and electrolyte secretion ( 180 ).

It is now apparent that guanylin and uroguanylin are also present in the centroacinar and ductal epithelial cells of the human ( 179 , 181 ) and rat pancreas ( 182 ). Also expressed in the same cells are the other components of this cell signaling system, GC-C, cGKII, and CFTR ( 179 , 181 , 182 ). Furthermore, activation of CFTR-like Cl − currents by guanylin and STA has been observed in CAPAN-1 cells ( 179 ). Thus, the possibility exits that guanylin and uroguanylin present within the ductal epithelial cells could, via a luminal pathway, activate HCO − 3 secretion. However, this hypothesis has not been tested directly by examining whether luminal guanylin and uroguanylin stimulate HCO − 3 and fluid secretion from isolated pancreatic ducts. Moreover, the physiologic stimulus for guanylin release from duct cells into pancreatic juice is unknown thus, the status of guanylin/uroguanylin as either a physiologic or pathophysiologic regulator of pancreatic ductal secretion remains to be established.

Question #a12ff

Silver nitrate and sodium chloride will react in aqueous solution to produce silver chloride, an insoluble solid that precipitates out of the solution, and aqueous sodium nitrate.

The balanced chemical equation that describes this double-replacement reaction looks like this

Silver chloride is a white insoluble solid that will precipitate out of the solution.

If you want, you can use the fact that silver nitrate and sodium chloride are soluble in water--the same can be said about sodium nitrate, the second product of the reaction--to write the complete ionic equation that describes this reaction.

#overbrace("Ag"_ ((aq))^(+) + "NO"_ (3(aq))^(-))^(color(blue)("AgNO"_ (3(aq)))) + overbrace("Na"_ ((aq))^(+) + "Cl"_ ((aq))^(-))^(color(blue)("NaCl"_ ((aq)))) -> "AgCl"_ ((s)) + overbrace("Na"_ ((aq))^(+) + "NO"_ (3(aq))^(-))^(color(blue)("NaNO"_ (3(aq))))#

If you eliminate the spectator ions, which are the ions present on both sides of the equation

#"Ag"_ ((aq))^(+) + color(red)(cancel(color(black)("NO"_ (3(aq))^(-)))) + color(red)(cancel(color(black)("Na"_ ((aq))^(+)))) + "Cl"_ ((aq))^(-) -> "AgCl"_ ((s)) darr + color(red)(cancel(color(black)("Na"_ ((aq))^(+)))) + color(red)(cancel(color(black)("NO"_ (3(aq))^(-))))#


Hemolymph Na + and Cl – concentrations

There were no significant differences in hemolymph Na + and Cl – levels between C. quinquefasciatus and C. tarsalis held in low-NaCl medium (250 μmol l –1 NaCl), and the values were not significantly different from tapwater values. There were no significant differences between species (Table 1).

Thirty minutes after transfer from 30 % sea water to 50 % sea water, both species experienced significant increases in hemolymph Cl – levels (P<0.04 Fig. 1). In C. quinquefasciatus, Cl – concentration continued to increase significantly throughout the first 6 h post-transfer and, at 24 h, remained at approximately 160 mmol l –1 . In contrast, hemolymph Cl – levels in C. tarsalis plateaued at hour 4 at 120 mmol l –1 , but then decreased somewhat at 6 h and fell to 97 mmol l –1 by 24 h. Hemolymph Cl – concentrations were significantly higher (P<0.001) in C. quinquefasciatus than in C. tarsalis by hour 4 post-transfer and remained significantly higher throughout the remainder of the experiment (P<0.001).

Unidirectional Na + and Cl – uptake rates

When both species were held in tapwater, C. tarsalis larvae had Na + uptake rates approximately twice as high as those of C. quinquefasciatus (Fig. 2A, P<0.0001), but there were no differences in Cl – uptake rates (Fig. 2B). In low-NaCl water (2 and 7 days of holding), Na + and Cl – uptake rates were not significantly different from those in tapwater, but species differences persisted in both Na + and Cl – uptake rates (P<0.001). Also, Na + uptake rates for C. quinquefasciatus and C. tarsalis were approximately two and six times those of Cl – uptake rates under all freshwater treatments. After 2 days in 30 % sea water, C. quinquefasciatus and C. tarsalis experienced a 6.7-fold (P<0.0001) and 2.7-fold (P<0.038) increase, respectively, in Na + uptake rates relative to tapwater values. Cl – uptake rates increased 8.4-fold in C. quinquefasciatus (P<0.0001) and sevenfold in C. tarsalis (P<0.0082). Na + uptake rates were double the rates for Cl – uptake in both species held in 30 % seawater medium. When larvae were transferred to 50 % sea water from 30 % sea water, Na + and Cl – uptake rates increased even further in C. quinquefasciatus (Na + P<0.0081, Cl – P<0.0001) and C. tarsalis (Na + P<0.001, Cl – P<0.0001). Uptake rates of Cl – , but not of Na + , were significantly higher in C. quinquefasciatus (P<0.021) than in C. tarsalis. Na + uptake rates approximated Cl – uptake rates in C. quinquefasciatus held in 50 % sea water, whereas Na + uptake was double that of Cl – uptake in C. tarsalis.

Unidirectional Na + and Cl – efflux rates

While being held in tapwater medium, Na + efflux rates were similar in both species (Fig. 3A) however, C. tarsalis had a Cl – efflux rate that was 50 % higher than that of C. quinquefasciatus (Fig. 3B P<0.0034). Rates of Na + and Cl – efflux were similar in the two species during freshwater holding. In contrast, when larvae were held for 2 days in the low-NaCl medium, C. quinquefasciatus had a Na + efflux rate that was significantly lower (P<0.0027) than that of C. tarsalis, but this rate was not significantly different from the tapwater value. There were no significant differences between Cl – efflux rates of larvae held in low-NaCl water versus tapwater and also no significant difference between species held in low-NaCl water. In 30 % seawater, Na + efflux increased approximately 4.2-fold (P<0.0003) in C. quinquefasciatus and 3.3-fold (P<0.0003) in C. tarsalis, but Cl – efflux rates did not change significantly in either species. Consequently, Na + efflux rates were 3.2- and 2.6-fold higher than Cl – efflux rates in C. quinquefasciatus and C. tarsalis, respectively. When the larvae in 30 % sea water were acutely transferred to 50 % sea water, C. tarsalis experienced a further 1.9-fold increase (P<0.0001) in the Na + efflux rate after 2 h, whereas the Na + efflux rate for C. quinquefasciatus did not change. The difference between the species was significant (P<0.014). Cl – effluxes increased significantly and to approximately the same rates in C. quinquefasciatus (P<0.0001) and C. tarsalis (P<0.0071) during the first 2 h in 50 % sea water. After hour 4, however, Na + effluxes had returned to 30 % seawater levels in both C. quinquefasciatus (P<0.0045) and C. tarsalis (P<0.0001) and were not significantly different between species. Similar trends were observed in the Cl – effluxes, with both species experiencing significant decreases (C. quinquefasciatus 38 %, P<0.0021 C. tarsalis 43 %, P<0.002). Throughout the 4 h of holding in 50 % sea water, Na + efflux rates were 2–3 times greater than the corresponding Cl – efflux rates in both species.

Freshwater Na + and Cl – uptake kinetic analysis

The relationship between Na + and Cl – uptake rates and external NaCl concentrations were examined in both species during holding in tapwater and low-NaCl medium. In tapwater and low-Na + medium, Na + uptake of both C. quinquefasciatus and C. tarsalis exhibited typical saturation kinetics (Fig. 4A,C) when external NaCl concentration was increased from 0.25 to 8 mmol l –1 NaCl. Michaelis–Menten kinetic analysis of the tapwater acclimation groups determined that the Na + uptake system of C. tarsalis had a maximum capacity (Jmax) that was almost double that of C. quinquefasciatus (confidence intervals did not overlap), but affinity values (Km) did not differ (Table 2). In contrast, the increase in Cl – uptake over the concentration range was linear in both species (Fig. 4B,D). When held in low-NaCl water, Na + uptake kinetics did not change in C. tarsalis larvae, whereas C. quinquefasciatus larvae exhibited a 54 % increase in Jmax (confidence intervals did not overlap), but no change in affinity (Table 2). Acclimation to low-NaCl medium did not affect the linear increase in Cl – uptake rates in either C. quinquefasciatus or C. tarsalis (Fig. 4B,D).

Who knew?

  • Due to its toxic properties, chlorine was used as a chemical weapon during World War I, according to the Royal Society of Chemistry.
  • When isolated as a free element, chlorine takes the form of a greenish-yellow gas, which is 2.5 times heavier than air and smells like bleach.
  • Chorine is the second-most-abundant halogen and the second-lightest halogen on Earth, after fluorine.
  • Sodium chloride (salt) is the most common compound of chlorine and occurs in large quantities in the ocean.
  • There may be some chlorine in the chicken you eat. Chicken carcasses that come from U.S. factory farms are often drenched in chlorine to get rid of fecal contamination.
  • Chlorine destroys ozone, contributing to the process of ozone depletion. In fact, one chlorine atom can destroy as many as 100,000 ozone molecules before it is removed from the stratosphere, according to the U.S. Environmental Protection Agency.
  • Swimming pools rely on chlorine to help keep them clean. According to the American Chemistry Council, the water in most swimming pools should contain two to four parts per million of chlorine. And that strong chlorine that you may smell when swimming at the public pool may actually be an indicator that additional chlorine is needed to balance the chemicals in the water.

Excess dietary salt may drive the development of autoimmune diseases

Increased dietary salt intake can induce a group of aggressive immune cells that are involved in triggering and sustaining autoimmune diseases.

This conclusion is the result of a study conducted by Dr. Markus Kleinewietfeld, Prof. David Hafler (both Yale University, New Haven and the Broad Institute of the Massachusetts Institute of Technology, MIT, and Harvard University, USA), PD Dr. Ralf Linker (Dept. of Neurology, University Hospital Erlangen), Professor Jens Titze (Vanderbilt University and Friedrich-Alexander-Universität Erlangen-Nürnberg, FAU, University of Erlangen-Nuremberg) and Professor Dominik N. Müller (Experimental and Clinical Research Center, ECRC, a joint cooperation between the Max-Delbrück Center for Molecular Medicine, MDC, Berlin, and the Charité &ndash Universitätsmedizin Berlin and FAU) . In autoimmune diseases, the immune system attacks healthy tissue instead of fighting pathogens.

In recent decades scientists have observed a steady rise in the incidence of autoimmune diseases in the Western world. Since this increase cannot be explained solely by genetic factors, researchers hypothesize that the sharp increase in these diseases is linked to environmental factors. Among the suspected culprits are changes in lifestyle and dietary habits in developed countries, where highly processed food and fast food are often on the daily menu. These foods tend to have substantially higher salt content than home-cooked meals. This study is the first to indicate that excess salt intake may be one of the environmental factors driving the increased incidence of autoimmune diseases.

A few years ago Jens Titze showed that excess dietary salt (sodium chloride) accumulates in tissue and can affect macrophages (a type of scavenger cells) of the immune system. Independent of this study, Markus Kleinewietfeld and David Hafler observed changes in CD4 positive T helper cells (Th) in humans, which were associated with specific dietary habits. The question arose whether salt might drive these changes and thus can also have an impact on other immune cells. Helper T cells are alerted of imminent danger by the cytokines of other cells of the immune system. They activate and "help" other effector cells to fight dangerous pathogens and to clear infections. A specific subset of T helper cells produces the cytokine interleukin 17 and is therefore called Th17 for short. Evidence is mounting that Th17 cells, apart from fighting infections, play a pivotal role in the pathogenesis of autoimmune diseases.

Salt dramatically boosts the induction of aggressive Th17 immune cells

In cell culture experiments the researchers showed that increased sodium chloride can lead to a dramatic induction of Th17 cells in a specific cytokine milieu. "In the presence of elevated salt concentrations this increase can be ten times higher than under usual conditions," Markus Kleinewietfeld and Dominik Müller explained. Under the new high salt conditions, the cells undergo further changes in their cytokine profile, resulting in particularly aggressive Th17 cells.

In mice, increased dietary salt intake resulted in a more severe form of experimental autoimmune encephalomyelitis, a model for multiple sclerosis. Multiple sclerosis is an autoimmune disease of the central nervous system in which the body's own immune system destroys the insulating myelin sheath around the axons of neurons and thus prevents the transduction of signals, which can lead to a variety of neurological deficits and permanent disability. Recently, researchers postulated that autoreactive Th17 cells play a pivotal role in the pathogenesis of multiple sclerosis.

Interestingly, according to the researchers, the number of pro-inflammatory Th17 cells in the nervous system of the mice increased dramatically under a high salt diet. The researchers showed that the high salt diet accelerated the development of helper T cells into pathogenic Th17 cells. The researchers also conducted a closer examination of these effects in cell culture experiments and showed that the increased induction of aggressive Th17 cells is regulated by salt on the molecular level. "These findings are an important contribution to the understanding of multiple sclerosis and may offer new targets for a better treatment of the disease, for which at present there is no known cure," said Ralf Linker, who as head of the Neuroimmunology Section and Attending Physician at the Department of Neurology, University Hospital Erlangen, seeks to utilize new laboratory findings for the benefit of patients.

Besides multiple sclerosis, Dominik Müller and his colleagues want to study psoriasis, another autoimmune disease with strong Th17 components. The skin, as Jens Titze recently discovered, also plays a key role in salt storage and affects the immune system. "It would be interesting to find out if patients with psoriasis can alleviate their symptoms by reducing their salt intake," the researchers said. "However, the development of autoimmune diseases is a very complex process which depends on many genetic and environmental factors," the immunologist Markus Kleinewietfeld said. "Therefore, only further studies under less extreme conditions can show the extent to which increased salt intake actually contributes to the development of autoimmune diseases."


It is commonly claimed in the popular evolutionary literature that the sea salinity level today is similar to that in cells and, therefore, this is evidence of abiogenesis and evolution . However, in a specialized computer search of over 15 million scientific articles, using the BIOSIS database accessed through OhioLink on March 15, 2010, I was unable to find a single article that scientifically supported this claim. The literature simply does not provide evidence for the supposition that the salinity level in the oceans gives credence to the abiogenesis theory of life’s origin in the sea. As Batten concludes:

Darwinists claim the fact that salt is necessary for life is a result of our having evolved in a sea environment. Creationists usually conclude that salt is common in the earth’s crust and in seawater because salt is required for our health. In the first case, the level of salt in life and the sea is similar because we are a product of nature. In the second case we live in a world created for us to meet our needs, thus nature was created to fit our requirements.

Given the evidence, the reason that sodium chloride is abundant is for the benefit of life as a result of design by the Creator has more credence than the claim that the putative similarity of the salinity of human blood and seawater is evidence that life originated in the sea by abiogenesis.

Synthesis: Carbon with Two Heteroatoms, Each Attached by a Single Bond Displacement of halogen atoms in alkyl and alkylidene halides by alkoxides and phenols

Tanimoto et al. studied the reactions of the polychlorinated ethanes ( 265)–(266 ) with an excess of sodium phenoxide in DMSO at 70 °C, which give the alkenes ( 267)–(268 ) < 76BCJ1931 >. The authors present good evidence that the reaction proceeds via initial dehydrochlorination to ( 269 ) and ( 270 ) and indeed ( 269 ) and ( 270 ) under the same reaction conditions give ( 267 ) and ( 268 ) in 78% and 28% yields respectively. Since the reactions of alkylidene halides with nucleophiles are much slower than those of alkyl halides, it is possible that the reactions of ( 265 ) and ( 269 ) involve the intermediary of the dichloro alkyne which then undergoes trans-addition of phenol to give the trans-1,2-dichloro-1-phenoxyethylene ( 267 ) as the sole product < 55JA3886 >. Further evidence for this route is provided by the observation of ‘small explosions’ during the reaction and the known propensity of this alkyne to explode.

The reaction of phenoxide with polyhalogenated ethylenes is in fact an old one. Slimmer reported in 1903 that potassium phenolate reacts with tribromoethylene to give a dibromo compound to which he initially gave the structure 1,1-dibromo-2-phenoxyethene ( 271 ) < 03CB289 >. Much later, Jacobs and Whitcher showed that the product was actually the 1,2-dibromo-1-phenoxyethene ( 272 ) < 42JA2635 >.

Sodium ethoxide reacts with trichloroethylene ( 273 ) in hot ethanol to give 1,2-dichloro-1-ethoxy-ethene ( 274 ) in 70% yield < 20JCS691 >. In the light of the structural problems described above it is of interest to note that the product of the reaction of sodium phenolate with trichloroethylene was proven to be ( 267 ) < 52M1 >. This means that the dichlorovinyl ethers described in a patent and whose structure was not defined, most probably are 1,2-dichloro-1-alkoxyethenes < 49BRP617820 >. This reaction was repeated by Normant and extended to that of sodium phenolate where it was necessary to use DMF as the solvent < 63BSF1876 >. Normant also reported that care had to be taken to prevent the release of the explosive and inflammable dichloroalkyne. The reaction of substituted phenols on ( 273 ) has also been conducted under phase-transfer conditions < 88PJC483 >. The reaction was stereoselective with only (E) isomers being produced a fact which was interpreted as showing that the reaction proceeded via dichloroalkyne ( Table 28 ).

Table 28 . Phase transfer catalysed reactions of substituted phenols with trichloroethylene to give (E)-1,2-dichloro-1-aryloxyethenes.

ArOHCatalystYield (%)
(4-HOC6H4)2CMe2PhCH2 + NEt3 − Cl62 a
(4-HOC6H4)2CMe2PhCH2 + NPr n 3 − Cl60 a
3,4-Me2C6H3OHPhCH2 + NPr n 3 − Cl51
4-EtC6H4OHPhCH2 + NPr n 3 − Cl50
3-MeC6H4OHPhCH2 + NPr n 3 − Cl58
4-NO2C6H4OHPhCH2 + NPr n 3 − Cl50

Tetrafluoroethylene reacts with sodium methoxide at 50–60 °C and 40 psi to give 1,2,3-trifluoro-1-methoxyethene ( 275 ) in 69% yield and with sodium phenoxide to give the phenyl ether ( 276 ) in 21% yield < 66USP3277068, 67ZOR1006, 68JOC816 >. Table 29 lists further examples of this type of displacement reaction.

Notably, the reaction of alkoxides with polyfluoro alkenes often leads not to displacement but rather to addition across the double bond. Thus ( 277 ), ( 278 ), ( 279 ) and ( 280 ) all give saturated ethers, for example ( 281 ), as the main products < 56JA1685 >.

Table 29 . Displacement reactions of unactivated polyhalo alkenes.

Instead of halide ions, a nitro group, for example in ( 282 ), may be displaced, as nitrite giving, for example the ethers ( 283 ) < 91ZOB56 >.

Clearly, displacement reactions should be much enhanced if the double bond also carries an electron-withdrawing group which would assist an initial Michael addition. This indeed is found. However, stopping the reaction after only one halogen has been displaced is difficult. Thus β,β-dichloroacrylonitrile ( 284 ) gives only the cyanoketene acetals ( 285 ) < 70JOC828 >. With care, however, it is possible to isolate by GLC the monosubstitution product ( 287 ) from 1,2,2-trichloroacrylonitrile ( 286 ) and methoxide < 71JOC3386 >.

Some insights into the mechanism of this reaction were provided by Burton and Krutzsch who showed that the halogenated styrenes ( 288 ) react with methoxide to give monomethyl ethers in up to 77% yield by displacement of chlorine with 90–96% stereospecificity < 71JOC2351 >. The results were rationalised in terms of an initial, irreversible, trans-addition of the nucleophile and electron pair across the double bond to give the short-lived carbanionic species. This then undergoes a rapid cis elimination of the chloride ion. Further examples of this reaction are given in Table 30 . A slightly different approach is that of Rossman and Muller who treated perfluoroisobutene ( 289 ) with trimethyltin methoxide to give 1,3,3,3-tetrafluoro-2-trifluoromethyl-1-methoxy-1-propene ( 290 ) in 62% yield < 93JFC(60)61 >.

Table 30 . Displacement reactions of activated halo alkenes.

a Generated in situ by addition of a mole of NaOMe to CF3CH(SOPh)CH3. b The (E) isomer was also isolated but no yield was given.

Watch the video: Natriumchlorid - Unser normales Kochsalz - #TheSimpleShort Gehe auf (May 2022).